Recent advances in CAR-T cell engineering

Abstract

Chimeric antigen receptor T (CAR-T) cell therapy is regarded as an effective solution for relapsed or refractory tumors, particularly for hematological malignancies. Although the initially approved anti-CD19 CART therapy has produced impressive outcomes, setbacks such as high relapse rates and resistance were experienced, driving the need to discover engineered CART cells that are more effective for therapeutic use. Innovations in the structure and manufacturing of CART cells have resulted in significant improvements in efficacy and persistence, particularly with the development of fourth-generation CART cells. Paired with an immune modifier, the use of fourthgeneration and next-generation CART cells will not be limited because of cytotoxic effects and will be an efficient tool for overcoming the tumor microenvironment. In this review, we summarize the recent transformations in the ectodomain, transmembrane domain, and endodomain of the CAR structure, which, together with innovative manufacturing technology and improved cell sources, improve the prospects for the future development of CART cell therapy.

Single-cell map of diverse immune phenotypes in the acute myeloid leukemia microenvironment

“…CLEC7A is a functional receptor in DC/Macrophage to enhance NK cells-mediated tumoricidal activity [ 41 ]. And high expression of TNFSF9 ( 4-1BBL ) also indicated this population might enhance T cell-mediated tumoricidal activity, as previously reported [ 42 ], but significantly corrected with poor prognosis puzzlingly (Fig. 2 g).…”

Recent progress of prognostic biomarkers and risk scoring systems in chronic lymphocytic leukemia

“…Novel agents, including inhibitors of B-cell receptor signaling pathway (ibrutinib, acalabrutinib, idelalisib and duvelisib) and the inhibitor of the antiapoptotic protein BCL-2 (venetoclax), are superior compared to conventional chemoimmunotherapy (CIT) regimens. Cellular immunotherapy with chimeric antigen receptor T-cell (CAR-T) and allogeneic stem cell transplant (allo-SCT) are available for high-risk patients [3][4][5][6][7][8][9]. New challenges emerge when patients relapse on novel agents, and optimal sequencing strategies have not been established.…”

T-cell-based Immunotherapies for Haematological Cancers, Part B: A SWOT Analysis of Adoptive Cell Therapies

“…Crossover targeting is only permissible without severe toxicity. Myelosuppression prevents myeloid malignancy CAR treatments since CD123 or CD33 are present on bone marrow stem cells (80). Antigen loss, such as in the case of CD19, may also induce treatment failure (81).…”